Natural regulatory mechanisms prevent inappropriate immune activation to self and innocuous foreign antigens. Here, we adapt the notion of immune privilege, which was originally applied to transplanted tissues, to consider how antigenic tumour cells and chronic pathogens might exploit natural regulatory mechanisms to become non-immunogenic. This conceptual approach reveals new mechanistic perspectives that may help to explain the paradoxical persistence of tumours and chronic pathogens, and suggests new opportunities to improve immunotherapy to treat these chronic inflammatory diseases.